PROJECT SUMMARY In the U.S., infants with open birth defects (spina bifida, gastroschisis, omphalocele) are more likely to have cesarean section (CS) deliveries than infants with any other type of birth defect. It has been proposed that CS may reduce the high risk of early death infants (e.g., by limiting trauma on the lesion and risk of infection). However, there is a lack of evidence to support or refute this theory in humans, and it is also not clear which other procedures or conditions influence mortality risk in infants with open birth defects. Therefore, a well-designed study is urgently needed to identify the optimal delivery procedures and conditions for these infants. A randomized control trial would be difficult to coordinate for relatively rare outcomes and would be difficult to justify in the absence of empirical evidence suggesting a benefit to CS. Therefore, an observational epidemiologic study design should be conducted, using a very large, population-based study sample to address differences in clinical referral patterns (i.e., selection bias); considering sufficiently homogenous and appropriate case-definitions (e.g., evaluating gastroschisis and omphalocele separately); addressing the potential for confounding; following-up during a long period (e.g., 1 year); and accounting for follow-up time in statistical analysis. We propose a two year study that meets these criteria using data from the Texas Birth Defects Registry for thousands of infants with open birth defects delivered between 1999-2011. We will use multivariable logistic regression to separately evaluate CS and several other obstetric procedures/conditions (forceps use, vacuum extraction, breech presentation, induction of labor, and prolonged labor) and risk for death by 28 days and age one for each of the three open birth defects. We will also consider the potential for effect modification by race/ethnicity, gestational age, and birth weight and the potential for confounding for several variables. Our findings will help determine the best clinical practices during labor and delivery for these infants and may ultimately reduce unnecessary invasive maternal procedures, and prevent infant deaths in this high-risk population.